Multi-site observational maternal and infant COVID-19 vaccine study (MOMI-vax): a study protocol

Background Pregnant women were excluded from investigational trials of COVID-19 vaccines. Limited data are available to inform pregnant and postpartum women on their decisions to receive a COVID-19 vaccine. Methods The goal of this observational, prospective cohort study is to evaluate the immunogenicity and safety of various Emergency Use Authorization (EUA) or licensed COVID-19 vaccines administered to pregnant or lactating women and describe the transplacental antibody transfer and kinetics of antibodies in mothers and infants. The study is adaptive, allowing additional groups to be added as new vaccines or vaccine regimens are authorized. Up to 20 clinical research institutions in the United States (U.S.) will be included. Approximately 200 pregnant women and 65 postpartum women will be enrolled per EUA or licensed COVID-19 vaccine formulation in the U.S. This study will include pregnant and postpartum women of all ages with and without chronic medical conditions. Their infants will be enrolled and followed beginning at birth in the pregnant cohort and beginning at the earliest possible time point in the postpartum cohort. Blood samples will be collected for immunogenicity outcomes and pregnancy and birth outcomes assessed among women and infants. Primary analyses will be descriptive and done by vaccine type and/or platform. Discussion Given the long-standing and legitimate challenges of enrolling pregnant individuals into clinical trials early in the vaccine development pipeline, this study protocol describes our current study and provides a template to inform the collection of data for pregnant individuals receiving COVID-19 or other vaccines. Trial registration NCT05031468. Supplementary Information The online version contains supplementary material available at 10.1186/s12884-022-04500-w.

Others may benefit in the future from information learned from the study.
The possible risks of participating in this study include those associated with having samples collected and the possibility of a breach of confidentiality.

BACKGROUND:
You are being asked to take part in this study because you recently had a baby(ies), and you have received or are scheduled to receive a vaccination series of any licensed or Emergency Use Authorization (EUA) COVID-19 vaccine. The COVID-19 vaccine is not given as part of this study.
While COVID-19 vaccines are being administered to women during pregnancy and post-partum, there is a need to understand the effect of maternal vaccination on the infant, including the possibility that infants could be protected from COVID-19. This study will help better understand how vaccination in pregnancy and in the post-partum period could benefit mothers and their infants.
By signing this consent, you are agreeing to your participation. Medical information about you is important to the study, so you will be asked to sign a release of medical records authorization form (this is what is on next page) to allow study staff to obtain necessary medical and delivery information.

RISKS OF THIS STUDY:
Blood draws: Pain, redness, or bruising at the site of the needle stick; rarely an infection. If you feel faint while having your blood drawn, you should lie down to avoid falling.
Breast milk collection (optional for breastfeeding mothers): Mild irritation from the cup on the breast pump or tenderness from milk expression.
Breach of confidentiality: The risk of breach of confidentiality related to your participation in this study is very low. Precautions are taken to protect the privacy of your personal information, including removing information that could be used to identify you. However as with any study, there is a potential risk of loss of confidentiality of your information. You may receive results of the blood and breast milk tests done as part of this study by the time the study ends. Also, the knowledge gained from this study may be used to inform future policy recommendations and personal decision-making about the use of approved COVID-19 vaccines in pregnant and lactating individuals. There is potential benefit to society resulting from insights gained from participation in this study due to the ongoing threat of the COVID-19 outbreak.
You do not have to be in this research study. You may choose not to be in this study without changing your healthcare, services, or other rights. You can stop being in this study at any time. If we learn something new that may affect the risks or benefits of this study, you will be told so that you can decide whether or not you still want to be in this study.

STUDY PROCEDURES:
Screening/Enrollment Visit (approximately 2 hours): If you agree to be in the study, you must first sign this informed consent form for yourself and a separate consent form for your baby(ies). We will then:  Ask you to sign a release of medical records authorization form  Get your contact information  Ask you questions to see if you can be in the study  Ask you about your medical, medication, obstetrics and respiratory illness history, including COVID-19 infections and vaccination  Record or calculate your BMI  Perform a brief physical exam, if needed  Draw about 2 teaspoons of blood  Schedule your next visit. If you: o Already received a COVID-19 vaccine: next study visit will be 2 months postpartum o Have an upcoming COVID-19 vaccine: next study visit will be 28 days after your last shot and will be approximately one hour. At that visit, we will:  Ask you about your medical, medication, obstetrics and respiratory illness history, including COVID-19 infections and vaccination  Perform a brief physical exam, if needed  Draw about 2 teaspoons of blood Optional for breastfeeding participants: If you are planning to breastfeed and agree to collect breast milk for this study, we will advise you on how to collect and store samples at follow-up visits. We will give you sample collection bags and a collection log to record the date when samples were collected. Unscheduled visits may take place as needed (for example if a sample is missed or there is an issue with processing a sample).

REASONS FOR INVESTIGATOR WITHDRAWAL:
You may be removed from the study if:  the study would present a health risk to you  you fail to follow the study requirements  the study stops or  you are no longer eligible for the study.

PARTICIPANT WITHDRAWAL:
Your participation in this study is completely voluntary. You can stop at any time. There is no penalty or loss of any benefits to which you are otherwise entitled if you choose not to enroll, stop, or change your mind. Always tell the study staff if you wish to stop. They will discuss any concerns about your safety, and whether you need any follow up or medical care.

SOURCE OF FUNDING:
Date of IRB Approval: 06/25/2021 This study is being funded by the NIH, NIAID, Division of Microbiology and Infectious Diseases. The research investigator is not being paid directly by the Sponsor. A payment will be made to the study center to cover the costs of the study procedures and the services provided by the research investigator and the study staff.

LABORATORY TESTING OF BLOOD AND BREAST MILK SAMPLES:
Research tests will be done on your blood and breast milk samples to measure immune response to COVID-19 vaccines. This means that we will measure your antibodies, which are proteins that the body uses to fight off the virus. We will also look at how different cells of your immune system help to fight the virus. The results of these tests are useful only for research purposes. No genetic testing will be done.
Blood and breast milk samples for these research tests may be sent to a central storage facility then sent to the research testing laboratories. The samples will not be labeled with your name or initials, or any other information that could readily identify you. The samples will be labeled only with a barcode and a unique tracking number (ID code) to help protect your confidentiality. Staff at the central storage facility and research testing laboratories will not know your identity, or even the study identifier you were assigned.
The clinical study staff will keep a list in a secure area with your name, contact information and the ID code (called a code key) that can link the samples to you, if needed. Access to the code key is limited to study staff working at the research site where your blood samples were collected.

STUDY RESULTS:
Individual research results may be provided to participants by the end of the study, but they will not be made available to your regular doctor and will not be placed in your medical record. Results from this study may be published while the study is ongoing and at the end of the study. Your individual identity will not be used in any reports or publications resulting from this study.

SECONDARY RESEARCH: What happens to the blood and breast milk samples after testing?
After all tests required for this study are done, we will save your leftover blood and breast milk samples at a central storage facility for possible secondary research. These samples may be shared for secondary Do not edit or delete research with investigators at the site, or with researchers at other sites or other institutions. Secondary research is research that is not part of this study and is not planned yet. There is no time limit on how long these samples will be stored.
Importantly, the samples and the information we collect about you and your baby(ies) will not be labeled with personal identifiers; they will only have an ID code on them. Reports from secondary research will not be kept in your health records or shared with you, unless required by law.
You do not have to agree to let us to save your samples for secondary research. If you choose not to let us to save these samples for secondary research, they will be destroyed when the study is over. Your medical care at this clinic will not be affected if you do not let us to save your samples for secondary research.
If you decide at any time that you do not want the samples stored for secondary research, you must contact study staff in writing who will then notify the laboratory/storage facility. They will mark your samples with a "Destroy" label and destroy them at the end of this study, or laboratory staff will take the samples out of storage and destroy them as soon as possible.

MATERNAL SAMPLES (blood and breastmilk, if provided) FOR SECONDARY RESEARCH
Please INITIAL whether or not your samples may be kept for use in secondary research: ______YES, my samples may be kept for secondary research.
______NO, my samples may not be kept for secondary research.

BREASTMILK SAMPLES
Breastmilk samples will be collected from lactating individuals who agree to provide samples as detailed above. You do not have to agree to give breast milk samples to participate in the study. Your medical care at the clinic where you were enrolled will not be affected if you decide not to give breast milk samples. Please INITIAL whether or not you agree to give breast milk samples as part of this study.
______ YES, I agree to give breast milk samples.
______ NO, I do not agree to give breast milk samples.